Hepatitis B is a viral infection that can cause serious liver disease. Chronic hepatitis B (CHB) infection places individuals at higher risk of developing cirrhosis of the liver and hepatocellular cancer. Immune dysfunction, including altered distribution and functional status of T cell immunity, is a contributor to hepatitis B virus (HBV) pathogenesis. In this study, we examined the distribution of circulating γδ T cell subpopulations and levels of cell surface expression of suppressive markers on γδ T cells in individuals with CHB infection and clinical liver disease. A significantly higher proportion of terminally differentiated (T_EMRA) (CD27⁻CD45RA⁺) γδ T cells along with significantly lower percentages of central memory (CD27⁺CD45RA⁻) and effector memory (CD27⁻CD45RA⁻) γδ T cells were observed in peripheral blood of these individuals. The expression of exhaustion markers-Tim-3 and Lag-3 was elevated in γδ T cells from CHB-infected individuals compared with healthy controls (HC) and blockade of these exhaustion markers resulted in restoration of interferon gamma (IFN-γ) secretion by γδ T cells. In addition, γδ T cells from CHB patients expressed increased levels of CD69, another important regulator of immune responses. Together, these results suggest that CHB patients with clinical sign of liver disease have T_EMRA γδ T cells with a potentially exhausted phenotype that may in turn impair their immunoregulatory role and facilitate pathogenesis of CHB disease.

中文翻译：

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有症状的慢性乙型肝炎感染患者循环γδT细胞的特征

乙型肝炎是一种病毒感染，可导致严重的肝脏疾病。慢性乙型肝炎 (CHB) 感染使个体面临更高的肝硬化和肝细胞癌风险。免疫功能障碍，包括 T 细胞免疫的分布和功能状态改变，是乙型肝炎病毒 (HBV) 发病机制的一个因素。在本研究中，我们检查了慢性乙型肝炎感染和临床肝病患者的循环 γδ T 细胞亚群分布和 γδ T 细胞抑制标记的细胞表面表达水平。终末分化 (T _EMRA ) (CD27 ⁻ CD45RA ⁺ ) γδ T 细胞的比例显着增加，而中央记忆 (CD27 ⁺在这些个体的外周血中观察到CD45RA ^- ) 和效应记忆 (CD27 ^- CD45RA ^{- ) γδ T 细胞。}与健康对照 (HC) 相比，来自 CHB 感染个体的 γδ T 细胞中衰竭标志物-Tim-3 和 Lag-3 的表达升高，并且这些衰竭标志物的阻断导致干扰素 γ (IFN- γ ) 分泌的恢复。 γδ T 细胞。此外，来自 CHB 患者的 γδ T 细胞表达的 CD69 水平升高，CD69 是免疫反应的另一个重要调节因子。总之，这些结果表明有肝病临床症状的 CHB 患者有 T _EMRA具有潜在耗尽表型的 γδ T 细胞可能反过来损害其免疫调节作用并促进 CHB 疾病的发病机制。